Multi-pass blood washing and plasma removal device and method

ABSTRACT

A blood washing and plasma separation device and method are disclosed, which utilize lumen-side fed hollow fiber membranes in multiple separation passes in conjunction with countercurrent flow wash injection.

This is a divisional of copending application Ser. No. 07/398,065 filedon Aug. 24, 1989, now U.S. Pat. No. 5,017,293.

BACKGROUND OF THE INVENTION

Filtration devices for the treatment of blood are known. For example,U.S. Pat. No. 4,498,990 discloses a cellular blood component/plasmaseparation device comprising two hollow fiber bundles situated coaxiallyto each other in a housing having blood inlet and outlet ports, afiltrate outlet port, and a replacement liquid port for supplying plasmamakeup of undisclosed composition (probably proteins and sugars) to thetreated blood prior to its reintroduction to the donor. U.S. Pat. No.4,668,399 discloses a single-pass nonwashing plasmapheresis module andprocess for use on whole blood (having a Hematocrit of about 35-45)having short hollow fibers with an effective length to lumen diameterratio of not greater than 300 in a steady state flow mode and notgreater than about 540 in a pulsed flow mode. U.S. Pat. No. 31,688 alsodiscloses a nonwashing single pass plasmapheresis non-hollow fibermembrane device. U.S. Pat. No. 4,631,050 discloses a batchautotransfusion system that, following macrofiltration of a patient'swhole blood and prior to a planar membrane separation of the plasma andcellular components, permits batch washing of the blood by mechanicalagitation with saline solution. U.S. Pat. No. 4,565,626 discloses adevice for removing toxins from blood that contacts the blood for aperiod of time with adsorbent material packed between hollow fibers,then withdraws the blood from the adsorbent; saline solution is used asa pressure-transmitting medium. Finally, U.S. Pat. No. 4,038,190discloses a fluid fractionation apparatus having two fiber bundles inseries with an externally-supplied fluid inlet port that permits a fluidto be supplied to the outside (as opposed to the lumen side) of thehollow fibers.

However, none of the foregoing devices addresses the need for anefficient combination blood component washing, concentration andseparation device capable of performing such operations in a continuousmode, and capable of operating on both whole and diluted blood, thelatter being encountered in surgical cavities as a result of the useduring surgery of saline wash to cleanse the surgical field.

The present invention meets such a need, thus providing a significantadvance in the art of blood filtration and treatment, as well asproviding other advantages and efficiencies which will become apparentfrom the detailed description which follows.

SUMMARY OF THE INVENTION

There are essentially two aspects to the present invention. In oneaspect, there is provided a combination cellular blood component washingand plasma removing device comprising elongate microporous hollow fibermembranes arranged into at least two discrete fiber bundles, the hollowfiber membranes permitting the permeation of at least a portion ofnon-cellular blood components through the walls thereof while preventingthe permeation of cellular blood components, a housing containing thefiber bundles, the housing having a blood inlet port, a plasma-depletedoutlet port, a plasma permeate port, and washing means for contactingcellular blood components with wash fluid and for removing the washfluid from the housing prior to the exit of cellular blood componentsfrom the plasma-depleted outlet port, wherein the lumens of the hollowfiber membranes of the fiber bundles are in fluid communication witheach other; the blood inlet port, the plasma-depleted outlet port, andthe washing means are all in fluid communication with the lumens of thehollow fiber membranes of the fiber bundles; and the plasma permeateport is in fluid communication with the outside of the hollow fibermembranes of the fiber bundles.

In the other aspect, the present invention provides a method ofsimultaneously washing and concentrating cellular blood components andremoving plasma from fluid blood having a Hematocrit (Hct) as low as 15(such as is encountered in surgical cavities during the course ofsurgery) comprising the steps of feeding fluid blood under pressure tothe lumens of elongate microporous hollow fiber membranes arranged intoat least two discrete fiber bundles, the hollow fiber membranespermitting the permeation of at least a portion of non-cellular bloodcomponents through the walls thereof while preventing the permeation ofcellular blood components, the lumens of the hollow fiber membranes ofthe fiber bundles being in fluid communication with each other;contacting the blood with wash fluid at least one point between discretefiber bundles; withdrawing a fluid containing wash fluid andnon-cellular blood components, including plasma, from the outside of thewalls of the hollow fiber membranes; and withdrawing a fluid containingcellular blood components in concentrated form from the lumens of thehollow fiber membranes of the last of the discrete fiber bundles.

The foregoing and other objectives, features, and advantages of theinvention will be more readily understood upon consideration of thefollowing detailed description of the invention, taken in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of an exemplary module embodying the features ofthe present invention.

FIG. 2 is a longitudinal cross section of an exemplary two-pass,one-wash module of FIG. 1.

FIG. 3 is a cross section of FIG. 2 taken on the line 3--3.

FIG. 4 is a longitudinal cross section of an exemplary three-pass, onewash module of FIG. 1.

FIG. 5 is a cross section of FIG. 4 taken on the line 5--5.

FIG. 6 is a longitudinal cross section of an exemplary three-pass,two-wash module of FIG. 4.

FIG. 7 is a cross section of FIG. 6 taken on the line 7--7.

DETAILED DESCRIPTION OF THE INVENTION

According to the present invention, there is provided a multi-passmodule, the essential features of which comprise at least two discretehollow fiber bundles arranged in series to separate blood plasma andcellular components with countercurrent cellular component washing meansbetween said bundles.

The hollow fiber membranes are fed whole or diluted blood through thelumens thereof to permit the permeation of at least a portion ofnon-cellular (plasma) blood components through the walls thereof, whilepreventing the permeation of cellular blood components, therebyeffecting separation of plasma and cellular components. Wash fluid isintroduced into the module at at least one point in fluid communicationwith the lumens of the hollow fibers to contact the cellular bloodcomponents with turbulence, causing a washing of the same.

Referring now to the drawings, wherein like numerals denominate the sameelements, FIGS. 1-3 show various views of an exemplary two-pass, onewash, blood washing and plasma removal device 10 of the presentinvention. Referring in particular to FIG. 2, the device 10 comprisestwo bundles 11a and 11b of elongate microporous hollow fiber membraneswhich are selective to the permeation of non-cellular blood componentsand prevent permeation of cellular blood components. The bundles 11a and11b are contained by a chamber or housing 12 and secured thereto bythermoplastic or thermosetting potting material 13. Housing end caps 12aand 12b are either integral with housing 12 or removable for ease ofmanufacture and cleaning. The housing, comprising elements 12, 12a and12b, has a blood inlet port 14, a plasma-depleted outlet port 15, aplasma permeate port 16, and a wash inlet port 17 and associated plenum18. Note that the arrangement of elements permits the inside or lumensof the hollow fiber membranes of both bundles 11 to be in fluidcommunication with each other, and that the lumens are also in fluidcommunication with blood inlet port 14, with plasma-depleted outlet port15, with wash fluid inlet port 17 and with the fluid inlet port'sassociated plenum 18; plasma permeate port 16 is in fluid communicationwith the outside of the hollow fiber membranes of both bundles 11.

FIGS. 4-5 show two cross sectional views of an exemplary three-pass, onewash, blood washing and plasma removal device 10' of the presentinvention, while FIGS. 6-7 show the same views of an exemplarythree-pass, two wash, blood washing and plasma removal device 10" of thepresent invention both 10' and 10" having a third hollow fiber bundle11c. Although only two- and three-pass modules are shown in drawingsherein, it should be understood that the present invention contemplatesinclusion of designs having more than three passes through hollow fibermembranes, the number of passes being equal to n, where n is ≧2; thenumber of washes contemplated is (n-m), where m is 1 or 2, with thelimitation that (n-m)≧1.

Suitable hollow fiber membranes 11 may be described as semipermeable,hydrophilic, polymeric and microporous. Hydrophobic fibers that havebeen rendered hydrophilic by chemical or physical treatment areacceptable as well. Examples include those made of treatedpolypropylene, polyethylene, polyvinyl alcohol, polyvinylidenefluoride,polymethylmethacrylate, and polysulfone. Internal diameter (ID) of suchhollow fiber membranes is preferably in the range of 200-400 microns,wall thickness is 50-150 microns, while average pore size is preferablyin the range of 0.1 to 1.0 micron, and porosity is from 25% to 80%.Fiber length is preferably between 30 and 100 cm, while the ratio ofeffective fiber length (L) to diameter (D) of the lumens is from about1000 to about 5000. A preferred potting material 13 is polyurethane, forexample, BIOTHANE 228, available from CasChem of Bayonne, N.J.

In operation, with reference to FIG. 2, blood having a Hematocrit as lowas 15, such as is encountered in diluted blood salvaged from a surgicalcavity, is fed via blood inlet port 14, to the lumens of the firstbundle of hollow fiber membranes, either under pressure or,alternatively, a vacuum is applied to the outside or "shell" side of thefibers via plasma permeate port 16, to create a transmembrane pressure(TMP) of from 100 to 500 mmHg. The flow rate is adjusted to a preferredrate of 100 ml/min, measured at the blood outlet port 15. Plasma, plasmaproteins, dissolved solutes, and any saline wash from a surgical cavity,comprising noncellular components of the blood, permeate from the lumensthrough the walls to the shell side of the first bundle of fibers 11a,ultimately passing out of the module via permeate port 16. A portion ofthe blood rich in cellular blood components (principally red and whiteblood cells and platelets, together with some hemoglobin and plasmaproteins), continues its passage through the lumens of the first bundleof fibers, thence into plenum 18, where it encounters wash solutionentering the module via wash port 17 and its associated plenum 18. Theintroduction of wash solution in a flow which is initiallycountercurrent to the flow of blood causes a turbulence between the two,resulting in a washing of the cellular components and a dilution ofhemoglobin from red blood cells. Because of the overall direction offlow and the applied transmembrane pressure, the cellular component-richblood, along with the injected wash solution, enters the lumens of thesecond bundle of fibers 11b where further concentration of the cellularblood components takes place by additional permeation and removal ofnon-cellular components, including the injected saline wash; inaddition, a portion of dissolved hemoglobin permeates the walls of thefibers and is separated via permeate port 16. Washed and concentratedblood having a substantially increased Hematocrit exits via blood outletport 15.

The same principles of operation apply to the exemplary embodiments ofthe invention shown in FIGS. 4 and 6, with the exception that twocountercurrent wash injection ports and associated plenums are used inthe embodiment shown in FIG. 6.

EXAMPLE 1

A two-pass, one wash module of substantially the same design as shown inFIG. 2 and having 4.5 ft² of membrane surface area was prepared withtreated hydrophilic polypropylene hollow fiber membranes totalingapproximately 90 cm in length, an ID of 330 microns, an average poresize of 0.6 micron, and a 70% porosity. The total, effective L:D ratiowas about 2700. The potting compound used was a blood-compatiblepolyurethane, and blood and wash ports and plenums 14, 15, 17 and 18were molded into end caps 12a and 12b. Dilute blood with an Hct of 22and a hemoglobin concentration (Hb) of 311 mg/dl was introduced to thelumens of the fibers of fiber bundle 11a via blood inlet port 14 at anaverage flow rate of 61 ml/min. The average flow rate, measured at theblood outlet port 15, was 18 ml/min, and an average TMP of 260 mmHg wasinduced by the application of a vacuum at permeate port 16. Sterilenormal saline solution was continuously introduced into wash port 17 andassociated plenum 18 at the average rate of 14 ml/min. Plasma recoveryfrom the plasma permeate port was calculated to be 89% of the plasma inthe feed blood, Hb was 93 mg/dl, while the Hct of blood collected fromblood exit port 15 was 64, representing a three-fold increase in Hct.

EXAMPLE 2

Whole blood having an Hct of 40 treated with the device of Example 1with substantially the same flow rates and TMP, yields a calculated Hctof 75 as measured at blood exit port 15. Plasma recovery is calculatedto be 78%.

EXAMPLE 3

A three-pass, one wash module of substantially the same configuration asshown in FIG. 4 was prepared in the same manner and with the samemembranes as in Example 1. The membranes of this Example, totalingapproximately 45 cm in length, had a total, effective L:D ratio of about1360.

Dilute blood feed with an Hct of 21 was introduced to the lumens of thefibers of fiber bundle 11a via blood inlet port 14 at an average flowrate of 72 ml/min. The average flow rate of the blood product, measuredat the blood outlet port 15, was 33 ml/min, and an average TMP of 310mmHg was induced by the application of a vacuum at permeate port 16.Sterile, normal saline solution was continuously introduced into washport 17 and associated plenum 18 at the average rate of 29 ml/min.Plasma recovery from plasma permeate port 16 was calculated to be 68%,while the Hct of blood collected from blood outlet port 15 was 46,representing greater than a two-fold increase in Hct. Hb in the bloodfeed was 385 mg/dl, while the Hb in the blood product was 223 mg/dl.

EXAMPLE 4

A three-pass, two wash module of substantially the same design as shownin FIG. 6 and having 6.8 ft² of membrane surface area may be prepared inthe same manner and with the same membranes as in Example 1, totalingapproximately 135 cm in length, and having a total effective L:D ratioof about 4100. Dilute blood feed with an Hct of 21 is introduced to thelumens of the fibers of fiber bundle 11a via blood inlet port 14 at anaverage flow rate of 128 ml/min. The average flow rate of the bloodproduct, measured at the blood outlet port 15, is 45 ml/min, and anaverage TMP of 360 mmHg is induced by the application of a vacuum atpermeate port 16. Sterile, normal saline solution is continuouslyintroduced into wash ports 17 and associated plenums 18 at the averagerates of 236 and 185 ml/min. Plasma recovery from plasma permeate portis calculated to be 82% while the Hct of blood collected from bloodoutlet port 15 is calculated to be 60, representing a threefold increasein Hct. Hb in the blood feed is 1002 mg/dl, while the calculated Hb inthe blood product is 118 mg/dl.

The terms and expressions which have been employed in the foregoingspecification are used therein as terms of description and not oflimitation, and there is no intention in the use of such terms andexpressions of excluding equivalents of the features shown and describedor portions thereof, it being recognized that the scope of the inventionis defined and limited only by the claims which follow.

What is claimed is:
 1. A combination cellular blood component washingand plasma removing device comprising means for enabling continuouswashings concentration and separating including(a) elongate microporoushollow fiber membranes arranged into at least two discrete fiberbundles, said hollow fiber membranes permitting the permeation of atleast a portion of non-cellular blood components through the wallsthereof while preventing the permeation of cellular blood components,(b) a housing containing said fiber bundles, said housing having a bloodinlet port, a plasma-depleted outlet port, a plasma permeate port, andwashing means for contacting said cellular blood components with washfluid and for removing said wash fluid from said housing prior to theexit of said cellular blood components from said plasma-depleted outletport,wherein the lumens of the hollow fiber membranes of said fiberbundles are in fluid communication with each other; said blood inletport, said plasma-depleted outlet port, and said washing means are allin fluid communication with the lumens of the hollow fiber membranes ofsaid fiber bundles; and said plasma permeate port is in fluidcommunication with the outside of the hollow fiber membranes of saidfiber bundles.
 2. The device of claim 1 wherein said washing meanscomprises at least one wash fluid inlet port and associated plenumadapted to permit mixing of said wash fluid with said blood.
 3. Thedevice of claim 2, having two discrete fiber bundles and one wash fluidinlet port with an associated plenum.
 4. The device of claim 2, havingthree discrete fiber bundles and one wash fluid inlet port with anassociated plenum.
 5. The device of claim 2, having three discrete fiberbundles and two wash fluid inlet ports with associated plenums.
 6. Thedevice of claim 5 wherein said two fluid inlet ports and associatedplenums are at opposing ends of said fiber bundles.
 7. The device ofclaim 2 wherein the ratio of effective fiber length to diameter of thelumens for said hollow fiber membranes is from about 1000 to about 5000.8. The device of claim 1 wherein the ratio of effective fiber length todiameter of the lumens for said hollow fiber membranes is from about1000 to about 5000.